The major focus of this Project has been to examine the potential adverse health effects[unreadable] resulting from prolonged inhalation exposure to brevetoxins. The inhalation toxicities of a complex mixture of[unreadable] brevetoxins and brevetoxin antagonists in K. brevis extract was examined in rats, and the toxicity of pure[unreadable] brevetoxin 3 was examined in both rats and mice. Substantial immune suppression in rats, as indicated by a[unreadable] reduction in antibody response to immunization with sheep red blood cells, was consistently the primary[unreadable] response observed. Suppression of antibody forming responses occurred in the absence of frank toxicity to[unreadable] the spleen, changes in lymphocyte populations, or T cell responses to antigen. This immune suppression is[unreadable] important in light of reports in increased emergency room visits for pneumonia during Red Tide episodes[unreadable] identified by Fleming project and decreases in alveolar macrophage function in sheep inhaling brevetoxins in project by Abraham. This[unreadable] proposal will address the following specific aims: (1) To define exposure concentration-response relationships[unreadable] for brevetoxin-induced effects on humoral immunity in rats and to examine the role of macrophage cathepsin[unreadable] inhibition in mediating these effects; (2) To examine the effects of brevetoxin inhalation on recovery from[unreadable] infection in a rat model of influenza including young adult and aged rats; and (3) To determine the immunotoxic[unreadable] potential of brevetoxin in offspring of dams inhaling brevetoxins. These investigations will broaden[unreadable] examination of the exposure concentration-response relationship for brevetoxin-induced effects on antibody responses to antigen, provide insight into the underlying mechanism(s) for the observed immune suppression,[unreadable] examine potential consequences to brevetoxin-induced immune suppression on responses to viral infection;[unreadable] and determine the potential developmental immunotoxicity resulting from perinatal brevetoxin exposure.